Open AccessAmyloid-β-Induced Mitochondrial Dysfunction
Author(s) -
John Xi Chen,
Shi Du Yan
Publication year - 2007
Publication title -
journal of alzheimer's disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.677
H-Index - 139
eISSN - 1875-8908
pISSN - 1387-2877
DOI - 10.3233/jad-2007-12208
Subject(s) - mitochondrial matrix , mitochondrion , mitochondrial permeability transition pore , reactive oxygen species , microbiology and biotechnology , blockade , neuroscience , chemistry , alzheimer's disease , biology , disease , biochemistry , medicine , receptor , programmed cell death , cytosol , enzyme , apoptosis
As an important molecule in the pathogenesis of Alzheimer's disease (AD), amyloid-beta (Abeta) interferes with multiple aspects of mitochondrial function, including energy metabolism failure, production of reactive oxygen species (ROS) and permeability transition pore formation. Recent studies have demonstrated that Abeta progressively accumulates within mitochondrial matrix, providing a direct link to mitochondrial toxicity. Abeta-binding alcohol dehydrogenase (ABAD) is localized to the mitochondrial matrix and binds to mitochondrial Abeta. Interaction of ABAD with Abeta exaggerates Abeta-mediated mitochondrial and neuronal perturbation, leading to impaired synaptic function, and dysfunctional spatial learning/memory. Thus, blockade of ABAD/Abeta interaction may be a potential therapeutic strategy for AD.